Development of anemia is a major problem in chronic renal failure. Its prevention/early treatment with recombinant human erythropoietin (rHuEpo) during pre-dialysis phase is important. Available iron is required for efficient action of rHuEpo; iron supplements are often needed; oral iron therapy is the preferred mode. Availability of oral iron varies widely in these patients; its efficacy cannot be ensured. We propose to develop a noninvasive method for direct assessment of the two steps that determine iron absorption: initial mucosal uptake (IMU), mucosal-serosal transfer (MST). Our approach is based on oral administration of a GelCap with known amounts of stable-isotope-labeled 58FESO4, the non-absorbable marker DyC13, and the visual marker brilliant blue to fasted patients, followed by laboratory analysis of the ratio 58Fe- Excess/Dy in the visually-marked sample of stool. Normalizing this ratio to the known intake of Dy yields IMU. Laboratory analysis of a blood sample taken two weeks later for 58Fe-Excess provides data for whole-body retention and the ratio of this to IMU is MST. We hypothesize that the inverse correlation between iron absorption (IMU and MST) and iron stores (as indicated by serum ferritin) is the basis for the widely variable absorption of oral iron in these patients; and that iron absorption can be enhanced by chronic ingestion of safe doses of ascorbic acid, and/or appropriate rHuEpo treatment. During Phase-I we will establish the feasibility of the approach by testing the following HYPOTHESIS: absorption of nonheme iron (IMU and MST) is inversely related to serumferritin in pre-dialysis patients, in 20 pre-dialysis patients with serum ferritin in the range expected in clinical practice. During Phase-II we will focus on how to optimize iron absorption (IMU and MST) by judicious administration of ascorbic acid and rHuEpo.